Devices containing gels, such as microfluidic devices, find use in many analytical detection techniques. For example, capillary electrophoresis is used for DNA profiling, analysis of pharmaceuticals, and detection and analysis of proteins and peptides.
A typical capillary for capillary electrophoresis is made of glass. Also used are polymeric materials, such as poly(dimethylsiloxane) (“PDMS”) silicone elastomer. The use and fabrication of PDMS devices are described by Effenhauser et al., “Integrated Capillary Electrophoresis on Flexible Silicone Microdevices: Analysis of DNA Restriction Fragments and Detection of Single DNA Molecules on Microchips”, Anal. Chem. (1997) 69, 3451–3457 which is incorporated herein by reference. An advantage of polymeric materials is fabrication costs are less than the fabrication costs with glass, and thus arrays of capillaries in a detection device or on a chip can be fabricated at lower cost with elastomers than glass. However, a limitation on use of PDMS and other polymeric material capillaries is they have less structural strength than glass.
Because of the lower structural strength of some polymeric capillaries, they cannot be used with high viscosity gels, because high pressures are required to introduce the gel into a microchannel. Thus many polymeric capillaries are limited to use with low viscosity gels or linear polymers as the separation fluid. High viscosity gels have advantages in some applications, particularly where high resolution is needed. For example, low viscosity gels are not effective for DNA sequencing on microchips, because high base-pair resolution is needed with relatively short separation channels, which requires a high viscosity gel.
Attempts have been made to form high viscosity gels in situ, starting with a low viscosity liquid. For example, chemically cross-linked gels have been used in capillary electrophoresis. However, in situ chemically cross-linked gels are difficult to fabricate inside capillaries, partly due to the shrinkage that occurs during the cross-linking reaction. In addition, the cross-linking chemistry includes an additional step in fabrication of the device, which increases cost. Furthermore, the gelation is irreversible, i.e., a matrix cannot be replaced after the formation of the gel.
An attempt was made to use temperature control to form a high viscosity gel in situ from a gel precursor with low viscosity. The gel precursor was designed so that a temperature change yields a high viscosity gel. See, Wu, C. H. et al. (1998), “Viscosity-Adjustable Block Copolymer for DNA Separation by Capillary Electrophoresis.” Electrophoresis 19(2):231–241. However, this techniques requires temperature control during the fabrication process, and results in a limited temperature range in which the device can be used. If the temperature changes, the gel can change properties and even become very fluid.
Accordingly, there is a need for an easy method of fabricating devices utilizing a high viscosity gel, without the need for the fabrication pressures associated with high viscosity gels, and where the device does not have a narrow temperature range in use.